The fibrosis in the liver which frequently occurs pari passu with chronic hepatocellular injury may arise as a result of increased collagen synthesis by connective tissue-derived cells which have migrated to the liver in response to the release of chemotactic factors. The nature of these putative chemotactic factors, their cell of origin and the sequence of events which leads to their release and biological activity are unknown. Using an in vitro assay to measure the response of smooth muscle cells (SMC) to chemotactic factors it has been shown that normal rat Kupffer cells (but not hepatocytes or hepatic endothelial cells) elaborate chemoattractants for SMC. It has also been shown that monocytes from chronic type B hepatitis blood but not from normal blood synthesize chemoattractants for SMC. These findings are consistent with the hypothesis that hepatic fibrogenesis can arise as a result of collagen synthesis by modulated SMC after their migration to the liver in response to the release of chemoattractants.